Chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells

Haisong Liu, Ronghui Li, Hsin-Kai Liao, Zheying Min, Chao Wang, Yang Yu, Lei Shi, Jiameng Dan, Alberto Hayek, Llanos Martinez Martinez, Estrella Nuñez Delicado and Juan Carlos Izpisua Belmonte ()
Additional contact information
Haisong Liu: The Salk Institute for Biological Studies
Ronghui Li: The Salk Institute for Biological Studies
Hsin-Kai Liao: The Salk Institute for Biological Studies
Zheying Min: Peking University Third Hospital
Chao Wang: The Salk Institute for Biological Studies
Yang Yu: The Salk Institute for Biological Studies
Lei Shi: The Salk Institute for Biological Studies
Jiameng Dan: The Salk Institute for Biological Studies
Alberto Hayek: UCSD-Medical School
Llanos Martinez Martinez: Universidad Católica San Antonio de Murcia
Estrella Nuñez Delicado: Universidad Católica San Antonio de Murcia
Juan Carlos Izpisua Belmonte: The Salk Institute for Biological Studies

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract Human pluripotent stem cell (hPSC)-derived pancreatic β cells are an attractive cell source for treating diabetes. However, current derivation methods remain inefficient, heterogeneous, and cell line dependent. To address these issues, we first devised a strategy to efficiently cluster hPSC-derived pancreatic progenitors into 3D structures. Through a systematic study, we discovered 10 chemicals that not only retain the pancreatic progenitors in 3D clusters but also enhance their potentiality towards NKX6.1+/INS+ β cells. We further systematically screened signaling pathway modulators in the three steps from pancreatic progenitors toward β cells. The implementation of all these strategies and chemical combinations resulted in generating β cells from different sources of hPSCs with high efficiency. The derived β cells are functional and can reverse hyperglycemia in mice within two weeks. Our protocol provides a robust platform for studying human β cells and developing hPSC-derived β cells for cell replacement therapy.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23525-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23525-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23525-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().